Hepatitis B virus pre-S deletion mutations are a risk factor for hepatocellular carcinoma: a matched nested case-control study.
A matched nested case-control study of 33 paired cases and controls was conducted, based on a study cohort in Long An county, Guangxi, China, to determine whether infection with hepatitis B virus (HBV) with pre-S deletions is independently associated with the development of hepatocellular carcinoma (HCC), without the confounding effects of basal core promoter (BCP) double mutations. The prevalence of pre-S deletions was significantly higher in HCC (45.5 %, 15 of 33) than the controls (18.2 %, 6 of 33) (P<0.01), under the control of the influence of BCP double mutations. Most of the pre-S deletions occurred in, or involved, the 5' half of the pre-S2 region and the difference between HCC (93.3 %, 14 of 15) and controls (66.7 %, four of six) was significant for this region (P=0.015). There was no significant difference in pre-S deletions between the BCP mutant group and BCP wild-type group (P>0.05), nor was the prevalence of pre-S deletions significantly different between genotypes B and C (P>0.1). These results suggest that pre-S deletions constitute an independent risk factor for HCC and their emergence and effect are independent of BCP mutations. The 5' terminus of pre-S2 is the favoured site for the deletion mutations, especially in HCC cases. Further prospective studies are required to confirm the role of these mutations in the development of HCC.
Fang
Zhong-Liao
ZL
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.|Department of Medicine, UCL Medical School, London W1T 4JF, UK.
Sabin
Caroline A
CA
Research Department of Infection and Population Health, Division of Population Health, UCL Medical School, University College London, London NW3 2PF, UK.
Dong
Bai-Qing
BQ
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.
Wei
Shao-Chao
SC
Sanitary and Antiepidemic Station of Long An, ChengXi Road, Cheng Xiang Town, Long An, Guangxi 532700, PR China.
Chen
Qin-Yan
QY
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.
Fang
Kong-Xiong
KX
Sanitary and Antiepidemic Station of Long An, ChengXi Road, Cheng Xiang Town, Long An, Guangxi 532700, PR China.
Yang
Jin-Ye
JY
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.
Huang
Jian
J
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.
Wang
Xue-Yan
XY
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China.
Harrison
Tim J
TJ
Department of Medicine, UCL Medical School, London W1T 4JF, UK.
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006509:Hepatitis B / Q000150:complications*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen